As it becomes eminently important to engineer products that disintegrate after their useful lifetime, we investigate a rising class of degradable polymers, poly(β-amino ester)s (PBAEs). PBAEs boast an impressively straightforward synthesis, easy incorporation of many functional groups, and hydrolytic degradability with lifetimes of hours to months. Leveraging this impressive class of polymers to address plastic waste pollution, facilitate controlled release of encapsulated compounds, and enable on-demand disintegration to template porous materials, will require both a thorough understanding of their degradation behavior and enhancements in functionality. Originally developed to complex negatively charged DNA for gene therapy, PBAEs contain a pH-dependent protonatable tertiary amine in each repeat unit. While the cationic properties of PBAEs are useful for complexing anionic molecules and imparting water solubility, protonation and deprotonation of the amines dramatically impact PBAE solution and degradation behavior. This complexity continues to frustrate efforts to predict and program PBAE degradation; indeed, some reports suggest that acidic conditions accelerate degradation, while others state the opposite. The high buffering capacity of PBAEs further complicates studying pH-dependent degradation as traditional buffers like 1X phosphate buffered saline can be ineffective at maintaining solution pH. Therefore, to unify understanding of PBAE degradation and solution properties, we studied PBAE hydrolysis as a function of pH and buffer concentration. We observe that, at low buffer concentrations relative to PBAE amines, the PBAE amines and the acid evolved during hydrolysis control solution pH. For example, dissolution of a PBAE at 20 mg/mL in 10 mM buffers with starting pH of 4, 6, or 8 all yield a solution pH &gt; 8, which gradually drops to <i>ca.</i> 4 as the polymer degrades. Meanwhile, at high buffer concentrations that afford relatively constant pH, hydrolysis rate increases with increasing pH, despite the reduced PBAE solubility. These studies showcase the role of buffering on the pH-dependent degradation and solution properties of PBAEs, providing guidance for the storage and use of PBAEs in applications ranging from drug delivery to thermosets. Towards expanding the application space of PBAEs, we will also discuss our work using clickable PBAEs to access previously restricted functionality such as anionic PBAEs for degradable polyelectrolyte complexes.

Connecting molecular features of poly(β-amino ester)s to their degradation and solution behavior to engineer functional materials with controlled lifetimes

ACS Spring 2022

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